4-Hydroxybenzyl cyanide

In 1903, Lapworth described his findings of the action of potassium cyanide on benzaldehyde [28], He postulated that cyanide adds to benzaldehyde to form V, followed by proton transfer of the a-labile hyd rogen, forming intermediate VI which is now referred to as an acyl anion equivalent. Addition to another molecule of benzaldehyde occurs to form VII (Scheme 1). The unstable cyanohydrin of benzoin VII then collapses to form benzoin and potassium cyanide. Additionally, Lapworth tested the reversibility of the addition of cyanide to benzaldehyde by first forming hydroxybenzyl cyanide (protonated variant of V) and subjecting it to benzaldehyde and base, in which benzoin was recovered. 

A specific cleavage reaction of NH2-terminal tyrosyl dipeptides occurred upon their treatment with DIB in methanolic potassium hydroxide. Tyrosine itself was converted into 4-hydroxybenzyl cyanide (52%) under these conditions [69], A related cleavage of tryptophan and several derivatives of it, including dipeptides, led to the formation of 3-methoxyindole [70]. Reserpine and also 2,3-dimethylindole reacted in the same way in the presence of alcohols, affording 3-alkoxyindolenines... 

Similarly, on mushroom tyrosinase-catalyzed oxidation of both 3,4-dihydroxy- and 4-hydroxybenzyl cyanides (334 and 335), the initially formed o-quinone (336) was converted into the corresponding quinone methide (337), which was not isolatable but was spectroscopically detected (Scheme 71) . 

Fig. 36. Mechanism proposed for inactivation of dopamine -hydroxylase by p-hydroxybenzyl-cyanide (16).

Reaction with tyrosine. Dilute chlorine water converts tyrosine (1) into. l-cliloro-4-hydroxybenzyl cyanide (2). Increased amounts of the reagent result It) conversion mainly into (3) and (4). On further reaction with chlorine water... 

Calculated k values according to eq. 8.26 and design VI (Fig. 8.4) are plotted in Fig. 8.8, against experimental values, for (i) five catecholamines (noradrenaline, adrenaline, adrenalone, dopamine, and isoprenaline) and thirteen mobile phases (0.035-0.150 M SDS and 0-15% 1-propanol), (ii) fifteen phenols (4-benzamidephenol, 4-hydroxy-benzyl alcohol, 4-hydroxyphenemethyl alcohol, 4-hydroxybenzyl cyanide, 4-hydroxyacetophenone, 4-hydro2 benzaldehyde, phenol, 4-fluorophenol, 4-... 

Figure 8.17 Chromatograms of a mixture of phenols in mobile phases containing 10% 2-propanol euid diverse CTAB molar concentrations (a) 0.12, (b) 0.10 and (c) 0.08. Peaks (1) 4-benzamidephenol, (2) 4-hydroxybenzyl alcohol, (3) 4-hydroxyphenemethyl alcohol, (4) 4-hydroxybenzyl cyanide, (5) 4-hydroxyacetophenone, (6) 4-hydroxybenzaldehyde, (7) phenol, (8) 4-fluorophenol, (9) 4-hydroxypropiophenone, (10) 4-methylphenol, (11) 4-nitrophenol, (12) 4-hydroxybenzophenone, (13) 4-isopropylphenol, (14) 4-hydroxydiphenyl-methane, and (15) 4-tert.-butylphenol. Reprinted from Ref. 11 with permission of Elsevier.

The effects of this inhibitor on the metabolism of A. fumigatus were very different from those of the other compounds used, since formation of all the characteristic acetate-derived phenols was strongly suppressed (Packter and Collins, 1974). Treatment of cultures gave a completely altered pattern and led unexpectedly to the secretion of atypical shikimic acid-derived phenols, including 2,3-dihydroxybenzoic acid, 4-hydroxyphenylpyruvic acid, and 4-hydroxybenzyl cyanide. In addition, the inhibitor was metabolized directly by transamination to fluorophenylpyruvic acid. 

An example of important non-volatile nitriles is 4-hydroxybenzyl cyanide, which is found in mustard pastes made from white mustard seeds Leucosinapis album) containing glucosinolate sinalbin. Nonvolatile nitriles also include cyanogenic glycosides, cyanogenic lipids and amino acids that contain the cyano group. 

Carney and Rinehart reported the results of additional feeding experiments in the marine sponge Aplysina fistularis in 1995 184). U- " C -L-tyrosine, U- C -L-3-bromotyrosine, and U C -L-3,5-dibromotyrosine were incorporated into both the dienone 1 and aeroplysinin-1 (14), and methyl- " C -methionine was specifically incorporated into the O-methyl group of aeroplysinin-1. In contrast to expectations, tyrosine was incorporated more efficiently than 3-bromotyrosine, which is in turn incorporated more efficiently than 3,5-dibromotyrosine. This may result from the bulky bromines interfering with the permeability of the precursors across cell membranes. It was surprising that methyl- " C -L-methyltyrosine, (methyl- C -L-3,5-dibromo-0-methyltyrosine, 3-bromo-4-hydroxybenzyl cyanide, and 3,5-dibromo-4-hydroxybenzyl cyanide were not incorporated into the dienone 1 and aeroplysinin-1 (14). Both 3-bromo-4-hydroxybenzyl cyanide and 3,5-dibromo-4-hydroxybenzyl cyanide have been identified as metabolites of A. fistularis 185), and their involvement as a potential precursor to the dienone 1 seems reasonable. The possible reasons for the lack of incorporation into 1 and 14, aside from the possibility of their not being part at the biosynthetic path, are poor transport of the halogenated nitriles across cell membranes, or poor solubility of the nitriles in sea water 184). 

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